Histopathologic features of melanoma in difficult-to-diagnose lesions: A case-control study

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Dermatopathology is considered the gold standard for melanoma diagnosis, but a subset of cases is difficult to diagnose by histopathology.


The goals of this study were to measure the accuracy of histopathologic features in difficult-to-diagnose melanocytic tumors and the interobserver agreement of those features.


This is a case-control study of histopathologic features of melanoma in 100 difficult-to-diagnose melanocytic neoplasms (40 melanomas and 60 nevi). Slides were blindly evaluated by 5 dermatopathologists. Frequencies, predictive values, and interobserver agreement were calculated. Univariate and multivariate logistic regression analyses were performed to identify the most influential features in arriving at a diagnosis of melanoma.


Asymmetry, single-cell melanocytosis, solar elastosis, pagetoid melanocytosis, and broad surface diameter were most influential in arriving at a diagnosis of melanoma. Asymmetry and single-cell melanocytosis were most predictive of melanoma. Fleiss kappa was <0.6 for interobserver agreement in 9/10 histopathologic features of melanoma.


This study is limited by the small sample size, selection bias, and binary classification of melanocytic lesions.


Our results indicate histopathologic features of melanoma in difficult-to-diagnose lesions vary in accuracy and reproducibility.

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